This proposal is concerned with evaluating the effects of long-term administration of phenytoin - an anticonvulsant and antiarrythmic drug commonly used in geriatric patients - on crucial adrenal functions in aged rats. Adrenal functions to be examined will include (i) corticosterone metabolism - synthesis and degradation and (ii) corticosterone secretion in response to stressful stimuli. The rat will be used as the animal model. In vivo metabolism and pharmacokinetic studies will be conducted in chronically cannulated animals to determine if the sysnthesis, secretion, degradation ad elimination of corticosterone - the major hormone of general homeostasis in the rat - is compromised by chronic pretreatment of the animal with phenytoin. Corroborative in vitro studies will be conducted. Data from this pilot study will be essential for subsequent studies on the mechanisms underlying any observed age-related, phenytoin-induced adrenal hypofunction. The long term objective of the proposed research is to assess the extent to which therapeutic agents commonly used in the geriatric population might impair essential biological functions such as homeostasis. It is hoped that the proposed studies will also contribute to the understanding of the extent to which maladjustment to stress accelerates the process of aging.